Cellular immune responses in the pathophysiology of preeclampsia

Abstract

Preeclampsia, defined as new‐onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi‐systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti‐angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal‐fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.

Integrated Analysis Identifies Four Genes as Novel Diagnostic Biomarkers Which Correlate with Immune Infiltration in Preeclampsia

“…The precise pathogenesis of preeclampsia remains elusive; nevertheless, endothelial aberrant function, improper angiogenetic activity, insufficient trophoblast invasive ability, and spiral uterine artery remodeling have been determined as pivotal contributing factors [ 28 , 29 ]. The improper stimulation of the intrinsic immunosystem and following inflammatory events can induce placental aberrant function or unsatisfactory maternal blood vessels' adaptative ability and facilitate the progression of the disease [ 30 , 31 ]. With the fast advancement of technologies, biological information has offered a potent method for selecting molecule biomarkers, and CIBERSORT kits have fostered the analyses of immunocyte infiltrative features of illnesses as well [ 32 ].…”

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

“…Gene ontology analysis of microarray showed that the immune response genes were down-regulated in the cKO uterus, suggesting the involvement of immune dysfunction in the abnormal placental formation ( Figure 3 A). It was reported that the cellular immune responses and major cellular subsets, such as regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils are involved in the pathogenesis of HDP [ 38 ]. Among them, NK cells were shown to directly interact with EVT and regulate their invasion and vascular reconstruction [ 37 ].…”

Clinical characteristics and laboratory data of pre-eclampsia patients with and without in vitro fertilization embryo transfer treatment

“…As is well known, pregnancy poses an immunological challenge [26]. Past few years have seen a rapid expansion of our knowledge of immune regulation in pre-eclampsia, and a hypothesis regarding the etiology of pre-eclampsia is the maladaptation of immune responses [27,28]. In this study, we wanted to determine whether there are differences in functional changes of innate immune cells between patients with and without IVF treatment.…”